Rosiglitasone and 15-deoxy-Δ12,14-prostaglandin J2 – PPAR γ agonists reduce microscopic changes in the liver in the course of chronic CsA treatment

Abstract

Cyclosporin A (CsA) belongs to immunosuppressant drugs known as calcineurin inhibitors that are used in connection with organ transplantation and in the treatment of autoimmune diseases. CsA use is often limited due to its toxic effects on the kidney, heart or the liver. Methods Male Wistar rats were treated subcutaneously with CsA (15 mg/kg) alone and in combination with one of PPAR γ agonists: rosiglitasone (8 mg/kg) or 15-deoxy-Δ 12,14 -prostaglandin J 2 (30 μg/kg) for 28 days. Twenty four hours after the last treatment, animals were sacrificed and blood was analyzed for total bilirubin, AST and ALT. Liver samples were fixed in 10% buffered formalin, processed and analyzed for microscopic changes. Results Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased in rats treated with CsA comparing to control animals. Total bilirubin level showed mild increase in 4/8 animals of CsA group. Liver samples in rats treated with CsA, when examined in light microscopy showed hepatic cord disorganization, focal degeneration and necrosis of single cells, sinusoidal congestion and dilatation, Kupffer cell activation. Interstitial fibrous tissue around bile ducts and central veins was focally oedematous. Mild mononuclear cell inflammatory infiltrates were seen accidentally within periportal area. Rosiglitasone and 15-deoxy-Δ 12,14 - prostaglandin J 2 significantly protected animals against CsA-induced functional and structural impairment of the liver.